Alzheimer Disease and Dementia
Dementia is a disorder characterized by a decline in cognitive ability to a point of interfering with daily function. The diagnosis can be challenging due to its insidious onset; early symptoms may only be apparent to close family members. Globally, the prevalence of dementia in individuals aged 60 and over is between 5%–8%. Of the 50 million people affected worldwide, approximately 60% live in low- to middle-income regions. Several specific syndromes fall under the category of dementia, including Alzheimer disease, vascular (multi-infarct) dementia, and Lewy body dementia.
Alzheimer disease (AD) is the most common cause of dementia in people older than 65 years. Memory impairment is its cardinal feature, with language and behavioral deficits occurring over time. In addition to age, family history appears to be a risk factor, suggesting a genetic link; the early-onset form of the disease seems to have the strongest genetic tie. The pathologic hallmarks of AD are extraneuronal amyloid plaques and neurofibrillary degeneration. These 2 findings are associated with neuronal death and decreased levels of the neurotransmitter acetylcholine. As the disease progresses, the basal forebrain and eventually the cerebral cortex become involved.
Diagnosis of AD is made clinically; serological testing and neuroimaging studies are used to rule out other causes. Epidemiological data from the European Community Concerted Action Epidemiology of Dementia Group (EURODEM) found that 70% of patients with dementia have AD. In 2015, the estimated global cost of the disease was $808 billion. Life expectancy in individuals with AD is shortened relative to the degree of impairment at the time of diagnosis. The disease presents significant challenges to family and caregivers in dealing with a variety of related issues, including emotional lability, risk of wandering, and potential for injury. Resources are available to assist patients and their families with these matters, such as the Alzheimer’s Association (www.alz.org).
An atypical presentation of AD can result from neuropathological abnormalities concentrated in particular areas of the brain. For example, posterior cortical atrophy can lead to progressive cortical impairment and ocular manifestations from pathology that involves the visual pathways. As a result, many of these patients may present early in the progression of their disease to an optometrist or ophthalmologist with a variety of visual symptoms and findings, including homonymous visual field defects.
Cholinesterase inhibitors such as donepezil and the neuropeptide-modifying agent memantine are helpful, used either alone or in combination therapy, in treating patients with AD. Studies investigating the potential benefit of vitamin E supplementation continue to show mixed results.
Vascular dementia is the second most common form of dementia and accounts for 10%–20% of cases in North America and Europe. The disease is associated with findings on neurologic examination consistent with prior strokes; neuroimaging studies typically show evidence of multiple infarcts. As in other vascular diseases, patients with hypertension, diabetes mellitus, or abnormal lipid profiles are at increased risk. Although donepezil and memantine are sometimes used in treatment, their benefit appears to be limited. Management is usually directed at treating any comorbidities, including the behavioral symptoms that often accompany this disease.
Lewy body dementia
Lewy body dementia (LBD) is another common form of neurodegenerative dementia. The disease is characterized pathologically by the presence of eosinophilic intracytoplasmic inclusions (Lewy bodies) in the deep cortical regions of the brain. There may be considerable clinical and pathologic overlap between LBD, AD, and Parkinson disease. Ophthalmologists should be aware of LBD, however, because patients with this syndrome often present with complex (or formed) visual hallucinations. The Dementia with Lewy Body Consortium has recently revised the criteria used to diagnose the disorder, including interpretation of certain biomarkers and the significance of the presence of an REM sleep behavior disorder in the patient. There are no specific pharmacotherapy options for patients affected, although cholinesterase inhibiters have shown some benefit in select cases.
Excerpted from BCSC 2020-2021 series: Section 1 - Update on General Medicine. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.